My first intuition was to provide a shortened input reference sequence to simulate from (basically the gene sequence in fasta format and the shortened corresponding GFF file). However, it doesn't solve the issue of simulating for several individuals with distinct isoform proportions.

My second thought was to simulate for each individual separately and to directly provide a LIB file, but I'm not sure how to simulate a good library and it would be redundant with what flux simulator is already doing.

Do you have any insight on this?

Thanks